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Interferon alpha-2a is an advantageous therapeutical alternative in case of severe uveitis due to Behcet disease (BD). It is administered subcutaneously 3 times a week at doses ranging from 3 up to...

CD4+CD25+Foxp3+ regulatory T (Treg) cells play a major role in peripheral tolerance. Multiple environmental factors and cell types affect their biology. Among them, activated effector CD4+ T cells can boost Treg cell expansion through TNF or IL-2. In this study, we further characterized this effector T (Teff) cell–dependent Treg cell boost in vivo in mice. This phenomenon was observed when both Treg and Teff cells were activated by their cognate Ag, with the latter being the same or different. Also, when Treg cells highly proliferated on their own, there was no additional Treg cell boost by Teff cells. In a condition of low inflammation, the Teff cell–mediated Treg cell boost involved TNF, OX40L, and plasmacytoid dendritic cells, whereas in a condition of high inflammation, it involved TNF and IL-2. Thus, this feedback mechanism in which Treg cells are highly activated by their Teff cell counterparts depends on the immune context for its effectiveness and mechanism. This Teff cell–dependent Treg cell boost may be crucial to limit inflammatory and autoimmune responses.

Prognostic factors are lacking in neurosarcoidosis (NS), and the association of immunosuppressive treatments with outcomes are unclear.To identify prognostic factors of and analyze the association of immunosuppressive treatment with relapse of NS.In this retrospective study, a cohort of 234 patients fulfilled the diagnostic criteria for NS in a tertiary referral center in Paris, France, from January 1, 1990, through December 31, 2015. The median follow-up was 8 years (range, 2 months to 23 years).All neurologic and extraneurologic data and treatments were analyzed. Functional outcomes measured by the absolute value and the variation from baseline of the Expanded Disability Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and relapse-free survival (RFS) were assessed. Analyses were stratified by the period of NS diagnosis (1990-1999 vs 2000-2015).The 234 patients undergoing assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42 years (interquartile range, 32-53 years). The probable 10-year survival rate was 89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI, 1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI, 2.31-19.7; P .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI, 1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for neurologic relapses. Encephalic involvement was associated with shorter neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P .001). A lower risk for relapse was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001), methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR, 0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60 months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR] per point, 1.92; 95% CI, 1.55-2.37; P .001), tobacco use (OR, 3.64; 95% CI, 1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI, 1.11-8.38; P = .03), and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04-8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months. Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated with worsening of the EDSS score at 60 months.This study identifies putative factors affecting morbidity and mortality in patients with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide, methotrexate, and infliximab) in these patients may be associated with lower relapse rates.

Pour citer cet article : Sève P, et al. Prise en charge diagnostique des uvéites : recommandations d'un groupe d'experts. Rev Med Interne (2017), http://dx.; International audience; Introduction. – La démarche diagnostique au cours des uvéites n’est pas standardisée. Elle doit prendre en compte l’épidémiologie des uvéites, cibler les affections les plus sévères et/ou les plus fréquentes, et/ou susceptibles de bénéficier d’un traitement spécifique. Ce travail a été réalisé afin de proposer des recommandations pour le diagnostic des uvéites.Méthodes. – Les recommandations ont été établies par un groupe de 15 experts, internistes, ophtalmo- logistes et rhumatologues, à partir d’une revue de la littérature et de l’étude ULISSE qui est la première étude prospective à avoir évalué une stratégie diagnostique pour les uvéites. Sont exclues de ces recom- mandations les uvéites de l’enfant, de l’immunodéprimé, les vascularites rétiniennes sévères et les entités purement ophtalmologiques.Résultats. – Le bilan paraclinique doit en premier lieu être orienté par les éléments de l’interrogatoire et les signes cliniques. La sérologie syphilitique est la seule sérologie systématique. Les sérologies toxoplasmose et herpès virus seront réalisées en cas de suspicion diagnostique et avant tout prélèvement oculaire. En l’absence de cause identifiée, nous proposons un bilan paraclinique orienté par les caractéristiques de l’uvéite. Il comporte un typage HLA B27 (uvéite antérieure aiguë unilatérale non granulomateuse), un dosage de l’enzyme de conversion de l’angiotensine, un test IFN-μ release assay (IGRA) et un scanner thoracique (uvéite chronique), une IRM cérébrale associée à une ponction de chambre antérieure avec dosage de l’interleukine 10 (uvéite intermédiaire ou postérieure après 40 ans). La rentabilité d’examens complémentaires non orientés est très faible.

The aim of the study was to assess the efficacy and safety of rituximab (RTX) for treating systemic lupus erythematosus (SLE)-associated immune cytopenias. This multicenter retrospective cohort study of adults from French referral centers and networks for adult immune cytopenias and SLE involved patients ≥18 years old with a definite diagnosis of SLE treated with RTX specifically for SLE-associated immune cytopenia from 2005 to 2015. Response assessment was based on standard definitions. In total, 71 patients, 61 women (85.9%), with median age 36 years [interquartile range 31-48], were included. The median duration of SLE at the time of the first RTX administration was 6.1 years [2.6-11.6] and the reason for using RTX was immune thrombocytopenia (ITP) for 44 patients (62.0%), autoimmune hemolytic anemia (AIHA) for 16 (22.5%), Evans syndrome for 10 (14.1%), and pure red cell aplasia for one patient. Before receiving RTX, patients had received a mean of 3.1 ± 1.3 treatments that included corticosteroids (100%), and hydroxychloroquine (88.5%). The overall initial response rate to RTX was 86% (91% with ITP, 87.5% with AIHA, and 60% with Evans syndrome), including 60.5% with complete response. Median follow-up after the first injection of RTX was 26.4 months [14.3-71.2]. Among 61 initial responders, relapse occurred in 24 (39.3%); for 18, RTX retreatment was successful in 16 (88.8%). Severe infections occurred after RTX in three patients, with no fatal outcome. No cases of RTX-induced neutropenia were observed. In conclusion, RTX seems effective and relatively safe for treating SLE-associated immune cytopenias.

BackgroundThe neuro-ophthalmological manifestations of Behcet’s disease (BD) are rare, and data regarding their characteristics and outcome are lacking.ObjectiveTo report prevalence, main characteristics and outcome of neuro-ophthalmological manifestations in BD.Patients and methodsThis is a retrospective monocentric study of 217 patients diagnosed with neuro-Behçet’s disease (NBD), of whom 29 (13.3%) patients presented with neuro-ophthalmological manifestations (55% of men and mean±SD age of 26±8 years). All patients underwent a detailed ophthalmological examination and were followed up in the internal medicine and the ophthalmology departments.ResultsNeuro-ophthalmological manifestations were the first presentation of BD in 45% of patients and developed later in the course of the disease in 55% of patients. They are divided into parenchymal (PM) and non-parenchymal (NPM)-related manifestations in, respectively, 13 patients (45%) and 16 patients (55%). PM included papillitis in seven patients (53.8%), retrobulbar optic neuritis in four patients (30.8%) and third cranial nerve palsy in two patients (15.4%). NPM included papilloedema related to cerebral venous thrombosis in all 16 patients, of whom 6 patients (37.5%) had sixth cranial nerve palsy. At initial examination, 93.1% of patients had visual alterations, including mainly decreased visual acuity visual field defects and/or diplopia. All patients were treated with corticosteroids and 79% of patients received immunosuppressive agents. After treatment, the visual outcome improved or stabilised in 66.7% of patients while it worsened in 33.3. The mean±SD logarithm of the minimum angle of resolution visual acuity improved from 0.4±0.3 at diagnosis to 0.2±0.3 after therapy. 10.3% and 3.4% of patients were legally blind at diagnosis and after therapy, respectively.ConclusionNeuro-ophthalmological manifestations of BD represented 13% of NBD. They could be potentially severe and disabling. Prompt treatment is the key factor in improving visual outcome.

Purpose: This study aimed to evaluate the safety and efficacy of anakinra for severe and refractory scleritis.Methods: Ten patients with severe (i.e. at least 2 ocular relapses per year despite treatment) and refractory [i.e. at least to one disease modifying antirheumatic drugs (DMARDS)] scleritis were treated with anakinra (100 mg/day subcutaneously). Scleritis was associated with inflammatory systemic diseases in 60% of cases. The remission rate defined the primary outcome.Results: Ninety percent of patients were complete responders with a mean follow-up of 19.4 months after starting anakinra. The corticosteroids daily dose decreased from 18.3 ± 4.1 mg to 4.2 ± 4.9 mg, (p < 0.05), at initiation of anakinra and at end of follow-up, respectively. Associated immunosuppressants were stopped in all cases except one. Side effects were observed in 4 patients who did not need anakinra withdrawal.Conclusions: This pilot study suggests the efficacy of anakinra in patients with refractory scleritis.

The efficacy of anti-TNFα agents has been recently evaluated in many studies in Behcet's disease (BD), particularly in ocular and life-threatening manifestations such as neurological and vascular disease. Areas covered: The following article aims to summarize the currently available efficacy and safety data of anti-TNFα agents in BD. Expert opinion: Most studies have shown dramatic and rapid efficacy with anti-TNFα agents on the main BD-associated issues including posterior uveitis, gastro-intestinal and neurological complications as well as major vessel disease. Experts in the field do recommend the use of anti-TNF agents (either infliximab or adalimumab) as a first-line therapy in severe posterior uveitis in BD and now use anti-TNFα treatment in BD-associated life threatening manifestations. However, data is mainly based on retrospective cohorts or open-label prospective studies. Controlled studies (versus conventional immunosuppressants such as azathioprine and cyclophosphamide) are warranted to properly evaluate their efficacy as first line therapeutic in life-threatening manifestations of BD.

Purpose of review More than 50% of hepatitis C virus (HCV) infected patients produce a mixed cryoglobulin and two-third of them will develop a symptomatic cryoglobulinemia vasculitis (CryoVas). In the present review, we aim at summarizing the most recent advances in diagnosis and treatment of HCV-CryoVas. Recent findings The treatment of HCV-CryoVas has much changed during the last months. The recent emergence of new direct-acting (DAA) interferon (IFN)-free antivirals, enabling high cure rates with a very good safety profile now permit to cure most patients with HCV-CryoVas. Multidisciplinary consensus recommends to consider IFN-free DAAs as first-line treatment for HCV-CryoVas patients. Immunosuppressive treatments (i.e. rituximab, glucocorticosteroids, cyclophosphamide and plasmapheresis) remain an interesting therapeutic approach, in severe form of HCV-CryoVas, failure or contradiction to antiviral treatments. Summary The great efficacy of DAA on HCV-CryoVas represents a major advance in clinical practice, as these new antivirals provide for the first time a well tolerated and definite treatment of such complication for most patients.

Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n = 32) or 24 weeks (n = 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse event or relapse of vasculitis.

Objective To evaluate the efficacy and safety of ustekinumab in the treatment of oral ulcers (OU) in patients with Behcet's disease (BD). Patients and methods Prospective study including 14 patients [median age of 39 (34; 41) years, with 71% of men] fulfilling criteria of the International Study Group for BD and with active OU resistant to colchicine. Patients received ustekinumab 90 mg (n = 11) or 45 mg (n = 3) subcutaneously at inclusion, at week 4, and every 12 weeks. The primary efficacy endpoint was the proportion of patients with complete response (CR), defined as no oral ulcer, at week 12. Results At week 12, 64% were in CR, 21% in partial response and 14% non-responders. The median number of OU decreased from 2 [2; 4] to 1 [0; 1.25] (p = 0.0005) at week 12. Mean change from baseline to week 12 of Behcet's syndrome activity score (BSAS) was 22.8 ± 0.3 (p = 0.01). The median daily corticosteroids dose decreased from 12.5 (10; 16.3) to 5 [5; 10] mg/day (p = 0.02). Three patients reported headaches, leading to discontinuation of ustekinumab in one case. After a median follow-up of 7 [3; 12] months, 10 (71%) patients were still receiving ustekinumab and four (28%) experienced a relapse. Decreased levels of circulating IL-17 and IL-12 [median [IQR]; 3.9 [1.6; 10.6] vs. 29.2 [25.2; 42.7] pg/ml, and 29.4 [23.1; 33.3] vs. 56.1 [51.1; 64.4] pg/ml, p = 0.008 for both] were observed under ustekinumab, respectively. Conclusion Ustekinumab seems to be efficient and safe for patient with BD and refractory OU although relapses are frequent.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is involved in KS and other tumors, including multicentric Castleman's disease and primary effusion lymphoma. Rituximab (RTX) is currently used for the treatment of several autoimmune or inflammatory diseases and humoral organ transplant rejection. De novo HHV-8 tumors induced by RTX used for these indications have not been reported previously. This study was undertaken to evaluate de novo HHV-8 tumors induced by RTX.In this retrospective study, we investigated the clinical, virologic, and pathologic features of 5 HIV-negative male patients with HHV-8 tumors induced by RTX therapy.Patients were all immunocompromised by previous treatments, which consisted of steroids and/or immunosuppressive agents, and received RTX for insufficient response, disease progression, or transplant rejection. They developed HHV-8 tumors a median of 4 months after beginning treatment with RTX (range 3-13 months). Four patients had at least 1 risk factor for HHV-8, including a high Fitzpatrick skin phototype (of3) (n = 3) and homosexuality (n = 1). Four patients developed KS (all 4 had skin lesions and 2 had visceral involvement), and 1 patient developed a solid primary effusion lymphoma. RTX was discontinued in all patients, and immunosuppressants were reduced when feasible. After a median follow-up of 20 months, 2 patients died. Remission of KS was complete in 1 patient and partial in 1 patient, and 1 patient had progression.Our findings indicate that patients who have a high skin phototype and are at risk of HHV-8 should be carefully screened for HHV-8 before RTX therapy. The safety of RTX, especially in nonlymphomatous disorders, should be carefully evaluated in patients at risk of HHV-8 tumors.

International audience; Hepatitis C (HCV) infection is associated with a morbidity and mortality due to liver complications. Hepatitis C infection is also frequently associated with rheumatic disorders such as arthralgia, myalgia, cryoglobulinemia vasculitis and sicca syndrome as well as the production of autoantibodies. The treatment of hepatitis C virus infection with interferon alpha (IFN) has been for long time contra-indicated in many rheumatologic autoimmune/inflammatory disorders. New oral IFN-free combinations offer an opportunity for HCV infected patients with extra-hepatic manifestations, including rheumatologic autoimmune/inflammatory disorders, to be cured with a short treatment duration and a low risk of side effects.

International audience; ObjectiveTo describe the features of exceptional coexisting Takayasu arteritis (TA) and sarcoidosis, two conditions of unknown cause associated with a common immunologic pattern.MethodsWe report seven cases of concomitant sarcoidosis-Takayasu or Takayasu-like vasculitis, observed in two referral centers between 1995 and 2015.ResultsAll patients were female. The mean age at sarcoidosis diagnosis and TA diagnosis was 36 and 37 years, respectively. Sarcoidosis occurred in 86% of cases before or together with TA. Sarcoidosis always had a classic expression except for one renal localization. Sarcoidosis was not severe and mostly non-treated (86%). In all cases of TA, supra-aortic arteries were involved; in only two TA cases a more diffuse inflammatory arterial involvement was noted. In one case, Takayasu arteritis occurred despite immunosuppressive therapy given for sarcoidosis. All patients received for TA a treatment with corticosteroids associated with methotrexate (four cases), infliximab (one case) or tocilizumab (one case). After a mean follow-up of 89 months, TA always improved and no death was observed.ConclusionsTA stands as pathology associated with sarcoidosis. TA occurred in three cases among 50. When sarcoidosis preceded TA, a recovery of sarcoidosis was achieved mostly without treatment. TA is a prognostic and therapeutic factor. Immunosuppressive treatment, including steroids, led to a good prognosis for TA as well as for sarcoidosis.

International audience; Background: The net benefits of new hepatitis C virus (HCV) direct acting antiviral drugs (DAA) in patients with cryoglobulinemia vasculitis (CryoVas) are unknown.Objective: To analyze the effectiveness and cost of all treatments used for HCV-CryoVas in the DAA versus pre-DAA era.Methods: A chart review of all HCV-CryoVas patients who received antivirals from 1993 to 2016 in a tertiary center was performed. Treatment effectiveness was analyzed for clinical, immunological and virological responses. Cost analyses included anti-HCV treatments, non-antiviral drugs, plasmapheresis, dialysis, and hospitalizations. We compared main data in the pre-DAA versus DAA period.Results: 201 HCV-CryoVas patients were included (women, 53.2%; mean age, 59.2 years; Metavir score F3-F4, 36.7%; genotype 1, 64.2%). Patients in the DAA era (n=27) compared to those in the pre-DAA era (n=174) showed higher rates of clinical (96.3% vs. 78.6%), immunological (89.5% vs. 77.1%), and sustained virological response (75.0% vs. 42.8%). Death rate was 14.8% vs. 24.4%, respectively. In the DAA compared to pre-DAA era, mean cost of anti-HCV drugs increased from 11,855 to 57,632 € while mean CryoVas-related cost decreased for both hospitalizations (from 33,510 to 21,347€) and non-antiviral treatments (from 17,347 to 11,397€).Conclusion: Improved antiviral efficacy of HCV drugs in the DAA era led to increased clinical and immunological efficacy and a lower death rate. Use of DAAs was associated to higher costs for HCV drugs while costs related to both hospitalizations and non-antiviral treatments decreased.

International audience; Background & AimsInterferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity.MethodsWe performed a prospective study of 27 consecutive patients with HCV-CV (median age 59 years) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France. Blood samples were collected from these patients before and after DAA therapy, and also from 12 healthy donors and 12 individuals with HCV infection without CV. HCV load, cryoglobulins, and cytokines were quantified by flow cytometry, cytokine multiplex assays, and ELISAs.ResultsTwenty-four patients (88.9%) had a complete clinical response of CV to DAA therapy at week 24, defined by improvement of all the affected organs and the absence of relapse. Compared to healthy donors and patients with HCV infection without CV, patients with HCV-CV, before DAA therapy, had a lower percentage of CD4+CD25hiFoxP3+ regulatory T cells (P

Pulmonary fibrosis (PF) is an uncommon manifestation observed in patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA). While patients with PF associated with AAV seem to have a worse prognosis, these patients have been described only in case reports or small retrospective case series. In this retrospective multicenter study, we report the main features and long-term outcomes of patients with PF associated with AAV, fulfilling the American College of Rheumatology criteria and/or Chapel Hill definitions. Forty-nine patients (30 men [61%]; median age at diagnosis of AAV, 68 [interquartile range, 58–73] years) with PF associated with AAV were identified. Forty (81.6%) patients had MPA and 9 (18.4%) had granulomatosis with polyangiitis. The diagnosis of PF preceded the onset of vasculitis in 22 (45%) patients. Usual interstitial pneumonia was the main radiologic pattern (n = 18, 43%). ANCA were mostly of antimyeloperoxidase specificity (88%). All patients were treated with glucocorticoids as induction therapy, combined with cyclophosphamide (CYC) (n = 36, 73.5%) or rituximab (RTX) (n = 1, 2%). Factors associated with mortality included occurrence of chronic respiratory insufficiency (hazard ratio [HR], 7.44; 95% confidence interval [CI], 1.6–34.5; p = 0.003), induction therapy with glucocorticoids alone (HR, 2.94; CI, 1.05–8.33; p = 0.04), and initial weigh loss (HR, 2.83; CI, 1.05–7.65; p = 0.041). The 3-year survival rate in patients treated with glucocorticoids alone or combined with an immunosuppressant (CYC or RTX) as induction therapy was 64% (95% CI, 41–99) and 94% (95% CI, 86–100), respectively (p = 0.03). After a median follow-up of 48 months [interquartile range, 14–88 mo], 18 (37%) patients died, including 11 related to respiratory insufficiency. PF is a rare manifestation of AAV with a very poor prognosis. Induction therapy with CYC might improve the outcome.

Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvements, more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, and neurological and gastrointestinal involvements. However, some patients still have refractory disease, relapse, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future biological therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of biotherapies provides the possibility of interfering with specific pathogenic pathways. Novel targeted biotherapies might be used in the future for BD.

Objective: To report the long-term outcome of neurological involvement in patients with Behcet's disease (BD). Methods: Retrospective analysis of 115 patients fulfilling the international criteria for BD [57% male with median [Q1-Q3] age of 37 [30-46] years] and with neuro-Behcet's disease (NBD) after exclusion of cerebral venous thrombosis. Factors associated with relapse of NBD, dependence and mortality were assessed. Results: Seventy-eight (68%) patients presented with acute NBD and 37 (32%) with a progressive course. The HLA B51 allele was carried by 49% of patients. Overall, 46/115 (40%) patients had a severe baseline disability status, represented by a Rankin score ≥ 3. The 5 and 7 years event-free survival rates were 65% and 53%, respectively. In multivariate analysis, a positive HLA-B51 status was independently associated with the risk of NBD relapse (OR=3.6 [1.5-9.1]). After a median follow-up of 73 [59-102] months, 21 (25.2%) patients became dependent or died. Factors independently associated with poor outcome were paresis at onset (OR=6.47 [1.73-24.23]) and a brainstem location of inflammatory lesions on MRI (OR=8.41 [1.03-68.43]). All 115 patients were treated with glucocorticosteroids, including 53/115 (46.1%) with cyclophosphamide and 40/115 (34.8%) with azathioprine. A trend towards longer event-free survival was observed in severe NBD patients (i.e. Rankin score ≥ 3 at onset) receiving intravenous cyclophosphamide compared with those treated with azathioprine (p =0.06). Conclusion: NBD is a severe condition in which patients with the HLA-B51 allele appear to experience a worse prognosis. © 2013 American College of Rheumatology.

Introduction: Treatment of mixed cryoglobulinemic (MC) vasculitis may target either the viral trigger hepatitis C virus (HCV) or the downstream B-cell arm of autoimmunity. This review will focus on advances in our understanding of the treatment of MC vasculitis. Areas covered: Aggressive antiviral therapy should be systematically considered for HCV–MC patients. As induction therapy, in mild to moderate MC patients and following rituximab in patients presenting with more severe disease. If failure or contraindication of antiviral therapy or in non-HCV cryoglobulinemia vasculitis, rituximab may be used alone. For patients presenting with the fulminant forms, including peripheral necrosis of extremities, rapidly progressive glomerulonephritis, digestive, cardiac, pulmonary and/or central nervous system involvement, apheresis can have immediate beneficial effects but must be combined with immunosuppression to avoid post-apheresis rebound of MC. High-dose steroids, rituximab, and sometimes cyclophosphamide com...

Les manifestations neurologiques de la maladie de Behcet (MB) sont retrouvees chez 5,3 a plus de 50 % des patients selon les series. Elles sont separees en deux grands types d'atteintes : les formes " parenchymateuses ", regroupant les atteintes intracerebrales (meningo-encephalites), par opposition aux formes " extra-parenchymateuses ", incluant les thromboses veineuses cerebrales et les anevrismes arteriels. Les atteintes medullaires et les atteintes peripheriques sont exceptionnelles. Un syndrome de neuro-Behcet (NB) doit etre evoque devant la survenue de troubles neurologiques, en particulier des cephalees et une atteinte pyramidale, chez un homme jeune suivi pour une MB. Neanmoins, sa reconnaissance est difficile lors des formes inaugurales (un tiers des cas), et necessite une connaissance des lesions morphologiques. Ainsi, les lesions de NB parenchymateux sont classiquement inflammatoires en IRM et situees a la jonction meso-diencephalique, ainsi que dans le tronc cerebral, avec rarement une extension sus-tentorielle. Une meningite associee n'est pas systematique, absente dans environ 30 % des cas. La physiopathologie de ces lesions est imparfaitement connue, mais l'infiltrat inflammatoire est majoritairement constitue de polynucleaires neutrophiles et de lymphocytes T actives (notamment de type Th17). Les principaux diagnostics differentiels concernent les pathologies infectieuses (herpes, listeriose, tuberculose), et inflammatoires (sclerose en plaques, sarcoidose) qui doivent etre systematiquement evoquees. Le traitement du NB doit etre initie des son diagnostic afin d'en limiter le risque de sequelles, de rechute ou de deces.

Behcet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, non-steroidal anti-inflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvement, a more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, neurological and gastrointestinal involvement. However, some patients still have refractory disease, relapses, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of immunomodulatory drugs provides the possibility of interfering with specific pathogenic pathways. Novel targeted immunosuppressive therapies might be used in the future for BD.

Vascular involvement is a common complication of Behcet's disease (BD) and affects up to 40% of BD patients. These complications worsen the prognosis of BD. The concept of vasculo-Behcet has been adopted for cases in which vascular complications dominate the clinical features. Vascular manifestations affect particularly young men, during the first years following onset of the disease. Venous complications are the most frequent vascular complications, affecting 14 to 40% of BD patients. Superficial and deep lower limb thrombosis is the most frequent venous complications but one third of venous thrombosis concern large vessels (such as cerebral venous thrombosis, pulmonary embolism, and inferior or superior vena cava, etc.). Budd-Chiari syndrome is the worst prognostic factor increasing mortality by 9 times. Arterial complications (2 to 17% of BD patients) include aneurysms and occlusions/stenosis. Main locations of arterial lesions are aortic (abdominal and thoracic), femoral, pulmonary and iliac arteries. Aneurysms are the most severe arterial complications, particularly pulmonary aneurysms associated with a high risk of massive bleeding. Cardiac complications (up to 6% of BD patients) include pericarditis, endocardial lesions (aortic regurgitation and less often mitral insufficiency), myocardial lesions (myocardial infarction, myocarditis and endomyocardial fibrosis) and intracardiac thrombosis (right ventricle and atrium). Coronary lesions complicated to myocardial infarction are the most severe cardiac complications. Treatment is based on corticosteroids and immunosuppressive drugs. The use of anticoagulation in venous thrombosis is still controversial.

Objective Hepatitis C virus (HCV) is associated with B cell lymphoproliferative disorders, including mixed cryoglobulinemia (MC) vasculitis and B cell non-Hodgkin's lymphoma. The expansion of clonal and autoreactive rheumatoid factor–bearing CD21−/low marginal zone (MZ) B cells was demonstrated in patients with HCV-associated MC vasculitis. Fc receptor–like (FCRL) proteins comprise a family of immunoregulatory proteins preferentially expressed on B lineage cells. The goal of this study was to investigate the expression of FCRL proteins 1–5 on B cells from patients with HCV-associated MC vasculitis. Methods Expression of FCRL proteins 1–5 was assessed by flow cytometry on B cells from 15 HCV-infected patients with type II MC (7 of whom had B cell non-Hodgkin's lymphoma), 20 HCV-infected patients without MC, and 20 healthy donors. To evaluate FCRL-5 as an immunotherapy target in HCV-associated MC vasculitis, 2 anti–FCRL-5 recombinant immunotoxins were produced using anti–FCRL-5 monoclonal antibodies and Pseudomonas exotoxin. Results Expression of FCRLs 2, 3, and 5 was markedly increased while expression of FCRL-1 was decreased on clonal CD21−/low MZ B cells, as compared with other B cell subsets, from HCV-infected patients and healthy donors. However, there was no difference in the pattern of FCRL expression between HCV-MC patients with lymphoma and those without lymphoma. The anti–FCRL-5 immunotoxins showed specific cytotoxicity against FCRL-5–expressing clonal CD21−/low MZ B cells isolated from HCV-infected patients as well as FCRL-5–transfected cell lines. No cytotoxicity against T cells or conventional B cells was observed. Conclusion These findings suggest that FCRL-5–targeting therapies could be a specific treatment for HCV-associated MC vasculitis and other FCRL-5–positive autoimmune B cell disorders.

International audience; Background: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome.Methods: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months.Results: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality.Conclusions: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.

International audience; No abstract available

Objective.Myocardial perfusion defects using scintigraphy have been frequently observed in patients with Takayasu arteritis (TA) without coronary stenosis. The aim of our study was to evaluate coronary microcirculation in TA using thallium-201 (201Tl) myocardial scintigraphy and dipyridamole (DPM) as vasodilator agent.Methods.Twenty-five consecutive patients with TA were prospectively recruited. They were asymptomatic for cardiac issues and examined using 201Tl myocardial scintigraphy at rest and after coronary artery vasodilation with intravenous DPM. Factors associated with improvement in myocardial perfusion after DPM were identified in patients with TA.Results.Among 25 patients with TA, 21 (84%) had 201Tl myocardial perfusion defects and 4 (16%) had normal resting myocardial perfusion. Using a 17-segments model for quantitative image analysis, DPM significantly improved resting 201Tl myocardial perfusion in 14 patients (61%) versus 9 patients without improvement (39%). We were able to examine coronary artery stenoses in 11 patients, including 10 patients with thallium perfusion defects, and significant coronary artery stenoses were present in only 2 patients (18.2%). No significant difference was found in traditional cardiovascular risk factors between TA patients with or without improvement of myocardial perfusion after DPM. The absence of improvement in myocardial perfusion after DPM tended to be closely associated with specific features and prognostic factors of TA, such as aortic regurgitation at diagnosis, renovascular hypertension, longer duration of TA disease, and male sex.Conclusion.We found the significantly high prevalence of myocardial perfusion defects mostly improved after vasodilation with DPM, which may indicate the major role of microcirculatory dysfunction in myocardial ischemia in TA.

Objective To describe the interplay between Behcet's disease (BD) and pregnancy. Methods This retrospective study included 76 pregnancies in 46 patients fulfilling the international criteria for BD. The median age of the patients at the time of entry into the study was 28.4 years (interquartile range 22.8–30.9 years). Patients were used as their own historical controls to assess the incidence of BD flares during pregnancy and before or after pregnancy. Factors associated with the occurrence of complications during pregnancy were assessed. Results Among the 76 pregnancies with BD analyzed, 27 (35.5%) were associated with worsening of the symptoms of BD flare; oral and genital ulcerations (78.4% and 67.6%, respectively) as well as ocular complications (32.4%) were the most frequent. The mean ± SD annual rates of BD flares were 0.49 ± 0.72 during pregnancy and 1.46 ± 2.42 during the nonobstetric period (P = 0.018). The proportion of BD flares tended to be lower in patients treated with colchicine (27.9% versus 45.4% of patients not treated with colchicine; P = 0.11). The overall rate of complications during pregnancy was 15.8%. The complications included miscarriage (5 patients), cesarean delivery (3 patients), medical termination of pregnancy (2 patients), hemolysis, elevated liver enzymes, and low platelets syndrome (1 patient), and immune thrombocytopenia (1 patient). There was a statistically significant association between a history of deep vein thrombosis in BD and the risk of obstetric complications (odds ratio 7.25, 95% confidence interval 1.21–43.46, P = 0.029). Neither gestational age at delivery nor neonatal outcome was influenced by BD. Conclusion The disease course in BD seems to improve during pregnancy, mostly in patients who are treated with colchicine. Pregnancy in patients with BD appears not to be associated with an increased rate of pregnancy-related complications.

Resume La tomographie par emission de positons au 18F-fluorodeoxyglucose (TEP-FDG) avait prouve son utilite dans l’arterite giganto-cellulaire, dans la maladie de Takayasu et dans les aortites indifferenciees. La TEP-FDG pourrait etre plus interessante que la tomodensitometrie (TDM) ou l’IRM dans la detection des stades les plus precoces de l’inflammation de la paroi vasculaire. Les donnees manquent quant a sa precision dans le diagnostic et le suivi des lesions vasculaires de la maladie de Behcet (MB). Nous rapportons le cas d’une femme âgee de 32 ans presentant une MB associee a une fievre d’origine inconnue, revelant des anevrismes volumineux de l’artere pulmonaire. La TEP-FDG a revele une fixation peripherique des anevrismes pulmonaires, soulignant l’etat inflammatoire de la paroi vasculaire de l’anevrisme. Notre patiente a ete traitee par corticoides et cyclophosphamide intraveineux, ce qui a induit une remission de sa MB. Durant le suivi, la TEP-FDG avait permis d’objectiver une reponse therapeutique favorable a quatre mois de traitement, alors que l’angio-TDM etait restee inchangee. Nous rapportons le premier cas decrivant l’utilite de la TEP-FDG dans l’evaluation therapeutique des anevrismes arteriels de la MB. D’autres etudes sont requises sur des cohortes plus larges afin de determiner la precision de la TEP-FDG chez les malades de Behcet avec une atteinte vasculaire.

International audience; BACKGROUND: The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon α (PegIFN)-α plus ribavirin and/or rituximab. About 30-40% of patients are non-responders or relapsers to such combination. OBJECTIVE: To analyse the safety and efficacy of Peg-IFNα/ribavirin/protease inhibitor combination in HCV-MC vasculitis. PATIENTS AND METHODS: Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFNα/ribavirin was associated to telaprevir (375 mg three times daily, for 12 weeks, (n=15)) or boceprevir (800 mg three times daily, for 44 weeks, (n=8)) for 48 weeks. RESULTS: The median age was 59 (52.5-66) years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06 g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15 g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). CONCLUSIONS: Peg-IFNα/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.

Objective Primary Sjogren's syndrome (SS) is an autoimmune disease associated with a high risk of developing non-Hodgkin's lymphoma. This study was undertaken to determine the nature of B cells driving lymphoproliferation in primary SS. Methods B cell subsets and function were analyzed in peripheral blood from 66 adult patients with primary SS (including 14 patients with B cell lymphoproliferative disease [LPD]) and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme-linked immunosorbent assay. Results We observed an expansion of an unusual CD21−/low B cell population that correlated with lymphoproliferation in patients with primary SS. A majority of CD21−/low B cells from patients with primary SS expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment, since their Ig genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21−/low B cells from patients with primary SS remained responsive to Toll-like receptor (TLR) stimulation. Molecules specifically expressed in CD21−/low B cells that are likely to induce their unresponsive stage were detected in gene array analyses. Conclusion Patients with primary SS who display high frequencies of autoreactive and unresponsive CD21−/low B cells are susceptible to developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.

Cardiac manifestation in primary systemic vasculitides is associated with poor outcomes, leading to the use of immunosuppressive therapy. In contrast, the spectrum and the outcome of cardiac involvement in the setting of mixed cryoglobulinemia vasculitis (CryoVas) have never been evaluated. To describe the clinical presentation and to evaluate clinical outcomes of cardiac manifestations during hepatitis C virus (HCV)-related mixed CryoVas, the clinical records of 165 consecutive patients with HCV-related mixed CryoVas followed from January 1, 1993, to January 1, 2010, were reviewed. Of the 165 patients with HCV-related mixed CryoVas, 7 (4%) had cardiac manifestations. Thoracic pain and congestive heart failure manifestations were the main clinical manifestations (n = 4 [57%] each). Cardiac imaging showed dilated cardiomyopathy in 5 patients and hypertrophic cardiomyopathy in 1. In multivariate analysis, patients with cardiac manifestations had more frequent B-cell lymphoma (odds ratio 18.1, 95% confidence interval 2.8 to 116.7, p = 0.0023) and gastrointestinal involvement (odds ratio 14.6, 95% confidence interval 2.0 to 104.9, p = 0.0078). All cardiac manifestations were reversible early after the initiation of corticosteroids and aggressive immunosuppressive therapy. However, after a median follow-up period of 19 months, 3 patients (43%) had died. Respective 6-month, 1-year, and 2-year survival rates in patients with and without cardiac involvement were 86% and 99%, 71% and 96%, and 48% and 90% (hazard ratio 5.01, p = 0.003). In conclusion, cardiac damage is a rare manifestation of HCV-related mixed cryoglobulinemia vasculitis. Cardiac involvement is associated with B-cell lymphoma and life-threatening manifestations. Despite favorable early outcomes, patients with cardiac damage had poorer survival than those without.

The off-label use of TNF antagonists in refractory sarcoidosis is increasingly reported but data on their efficacy and safety are still insufficient.To report on efficacy and safety of TNF antagonists in severe and refractory sarcoidosis.Examination of retrospective demographic, clinical, therapeutic, and adverse event data on 132 sarcoidosis patients (58% women; mean (min-max) age = 45.5 (14-78) years) given TNF antagonists (mainly infliximab, 91%) and investigation of response-linked factors.The overall clinical response (complete and partial) rate was 64%. TNF-antagonist efficacy (i.e., significant decrease of the ePOST score) was noted in cases with neurologic, heart, skin, and upper respiratory tract involvements. No significant difference in efficacy was found between anti-TNF used alone and TNF with immunosuppressant. The use of anti-TNF allowed reducing prednisone dosage at end of follow-up (p0.001). Adverse events were observed in 52% of the patients; they included infections (36%) and allergic reactions (8%) and required treatment interruption in 31 cases (23%). When TNF antagonists were interrupted, 13 patients experienced relapses within 14 months on average (median follow-up: 20.5 months).TNF antagonists were efficacious in about two-thirds of patients with severe/refractory sarcoidosis but their use led to a high rate of adverse events.

We thank Moiseev et al for their interest in our work regarding sofosbuvir and ribavirin in hepatitis C virus (HCV)-associated mixed cryoglobulinemia vasculitis (VASCUVALDIC study)1 and to bring new elements for discussion. Moiseev et al emphasise that treatment with immunomodulatory or immunosuppressive therapy (including rituximab) may have contributed to the impressive results of the VASCUVALDIC study. We have to stress that with the advent of new direct-acting antiviral (DAA) drugs (ie, sofosbuvir plus ribavirin), up to 87.5% of patients achieved complete clinical remission while only 17% of patients required the use of rituximab and glucocorticosteroids associated with antiviral therapy.1 In comparison, first-generation protease inhibitors …

Central and peripheral B cell tolerance checkpoints are defective in many patients with autoimmune diseases, but the functionality of each discrete checkpoint has not been assessed in patients with Sjögren's syndrome (SS). We undertook this study to assess this functionality in SS patients.Using a polymerase chain reaction-based approach that allows us to clone and express, in vitro, recombinant antibodies produced by single B cells, we tested the reactivity of recombinant antibodies cloned from single CD19+CD21We found that the frequencies of newly emigrant/transitional B cells expressing polyreactive antibodies were significantly increased in SS patients compared to those in healthy donors, revealing defective central B cell tolerance in SS patients. Frequencies of mature naive B cells expressing autoreactive antibodies were also significantly increased in SS patients, thereby illustrating an impaired peripheral B cell tolerance checkpoint in these patients.Defective counterselection of developing autoreactive B cells observed in SS patients is a feature common to many other autoimmune diseases and may favor the development of autoimmunity by allowing autoreactive B cells to present self antigens to T cells.

Objective Aortitis is an exceedingly rare manifestation of tuberculosis. We describe 11 patients with tuberculous aortitis (TA). Methods Multicenter medical charts of patients hospitalized between 2003 and 2015 with TA in Paris, France, were reviewed. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. TA was considered when aortitis was diagnosed in a patient with active tuberculosis. Results Eleven patients (8 women; median age, 44.6 years) with TA were identified during this 12-year period. No patient had human immunodeficiency virus infection. Tuberculosis was active in all cases, with a median delay of 18 months between the first symptoms and diagnosis. At disease onset, vascular signs were mainly claudication, asymmetric blood pressure, and diminished distal pulses. Constitutional symptoms or extravascular signs were present in all patients at some point. Aortic pseudoaneurysm was the most frequent lesion, but three patients had isolated inflammatory aortic stenosis. TA appeared as extension from a contiguous infection in only three cases. Tuberculosis was considered because of clinical features, tuberculin skin or QuantiFERON-TB Gold (Quest Diagnostics, Madison, NJ) test results, pathologic findings, and improvement on antituberculosis therapy. A definite Mycobacterium tuberculosis identification was made in only three cases. All patients received antituberculosis therapy for 6 to 12 months. Surgery including Bentall procedures, aortic bypass, and open abdominal aneurysm repair was performed at diagnosis in eight patients. Seven patients received steroids as an adjunct therapy. All patients clinically improved under treatment. No patients died for a median follow-up duration of 4 years. Conclusions TA may result in aneurysms contiguous to regional adenitis but also in isolated inflammatory aortic stenosis. Steroids may be associated with antituberculosis therapy for inflammatory stenotic lesions. Surgery is indicated for aneurysms and in case of worsening stenotic lesions despite anti-inflammatory drugs. No patient died after such combined treatment strategy.

Purpose: To retrospectively assess the frequency of ocular relapse and the possibility of long-term remission in patients treated with interferon (IFN) for severe uveitis associated with Behcet disease.Methods: All patients were treated with an initial dosage of 3 million IU IFN three times a week. The main outcome measure was the number of relapses per person per year before, during, and after IFN treatment.Results: Of 36 patients (67 eyes), 31 (86.1%) responded to IFN. The mean follow-up was 8.19 years. Twenty-one out of 36 patients discontinued IFN and 76% of these have not relapsed within 5.05 years after discontinuation. The mean relapse per person per year decreased significantly from 1.39 to 0.0496 (p = 1.82×10−10) during the treatment period and remained at 0.057 relapses per person per year after IFN discontinuation.Conclusion: IFN efficiently decreases the relapse rate and seems to permit long-term remission even after discontinuation.

International audience; Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P

Backgroung: This study investigated the efficacy and safety of TNF antagonists in sarcoid uveitis in unselected cases. Design: This is a multicentre study on patients with sarcoidosis who received TNF antagonists in pneumology and internal medicine departments in France. We present here the subgroup of patients with biopsy-proven sarcoid uveitis included in the nationwide registry STAT (Sarcoidosis treated with TNF AnTagonists). Results: Among the 132 patients included in this multicenter study, 18 patients with refractory uveitis were treated as a first-line TNF antagonist with infliximab (n=14), adalimumab (n=3) and certolizumab (n=1). Before anti-TNF initiation, the median duration of sarcoidosis was 42 months and 83% of the patients have been treated with at least one immunosuppressive drug. Six patients switched for a second-line TNF antagonist. After a mean time under treatment of 29 months, the treatment resulted in a significant decrease of the ophthalmic extrapulmonary Physician Organ Severity Tool (ePOST) (mean score: 4.2 vs. 2.6) scores and a steroid sparing effect (29.4±20.7 vs. 6.2±5.2 mg/d). Overall, the ophthalmic response, either complete or partial, was 67%. Nine patients (50%) presented adverse events, including severe infectious complications in 5 patients, which required anti-TNF treatment interruption in 6 cases (33%). Among the 7 responder patients who discontinued anti-TNF therapy, 71% relapsed. Finally, 12 patients (67%) could continue TNF antagonist treatment. Conclusions: TNF antagonists were efficient in 67% of biopsy-proven refractory sarcoid uveitis. Severe adverse events, mainly infectious complications, were frequent. The high frequency of relapses after anti-TNF-α discontinuation requires a close patient follow-up thereafter. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 74-80)

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV.

International audience; During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined.